Nuphar alkaloids, originally isolated from water lilies, induce apoptosis in mammalian cells in less than 1 h, making them possibly the fastest known inducers. However, the mechanism by which this rapid apoptosis occurs remains unknown. We have investigated canonical aspects of apoptosis to determine how the nuphar alkaloid, (+)-6-hydroxythiobinupharidine (6HTBN), induces apoptosis. 6HTBN induced rapid apoptosis in various leukemia, lymphoma, and carcinoma cell lines, suggesting that its mechanism is cell-type independent. It also circumvented resistance of patient-derived chronic lymphocytic leukemia cells generated by co-culture on survival-promoting stroma. Intriguingly, 6HTBN failed to induce apoptosis in platelets. The mechanism of apoptosis involves activation of caspase 9 and caspase 3, but not caspase 8 as previously reported. The release of cytochrome c from mitochondria occurred even in the absence of BAX/BAK and in cells that retained mitochondrial membrane potential. These results suggest a novel mechanism of apoptosis that has previously not been reported. The molecular target of the nuphar alkaloids remains to be determined.

中文翻译：

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Nuphar生物碱通过新型的caspase依赖性但BAX / BAK依赖性途径诱导非常快速的凋亡。

最初从睡莲中分离出来的Nuphar生物碱可在不到1小时的时间内诱导哺乳动物细胞凋亡，因此可能是已知最快的诱导剂。然而，这种快速凋亡发生的机制仍然未知。我们已经研究了凋亡的规范方面，以确定nuphar生物碱（+）-6-羟基硫代双吡啶（6HTBN）如何诱导凋亡。6HTBN在多种白血病，淋巴瘤和癌细胞系中诱导快速凋亡，提示其机制与细胞类型无关。它也规避了通过共培养对生存促进的基质产生的患者来源的慢性淋巴细胞白血病细胞的耐药性。有趣的是，6HTBN未能诱导血小板凋亡。凋亡的机制涉及caspase 9和caspase 3的活化，但不涉及caspase 8的活化。即使不存在BAX / BAK以及在保留线粒体膜电位的细胞中，细胞色素c也从线粒体释放。这些结果表明以前没有报道过的新的凋亡机制。Nuphar生物碱的分子靶标尚待确定。